Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA

Eun Jin Lee, Eduardo A. Groisman

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages. This compartment must be acidified for Salmonella to survive within macrophages, possibly because acidic pH promotes expression of Salmonella virulence proteins. We reasoned that Salmonella might sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor but also by an increase in cytosolic ATP levels, because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis. Here we report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly induced horizontally acquired gene when Salmonella is inside macrophages. This transcript is induced both upon media acidification and by physiological conditions that increase ATP levels independently of acidification. ATP is sensed by the coupling/uncoupling of transcription of the unusually long mgtC leader messenger RNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader messenger RNA that eliminates the response to ATP hinders mgtC expression inside macrophages and attenuates Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader messenger RNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.

Original languageEnglish
Pages (from-to)271-275
Number of pages5
Issue number7402
Publication statusPublished - 2012 Jun 14
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements We thank C. Turnbough for discussions, M. Wade for help with the mouse virulence assays, and R. Breaker and A. Roth for help with in-line probing experiments. This work was supported, in part, by grant AI49561 from the National Institutes of Health to E.A.G., who is an investigator of the Howard Hughes Medical Institute.

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA'. Together they form a unique fingerprint.

Cite this